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XCR1

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Target id: 75

Nomenclature: XCR1

Family: Chemokine receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 333 3p21.31 XCR1 X-C motif chemokine receptor 1 6,11
Mouse 7 322 9 74.71 cM Xcr1 chemokine (C motif) receptor 1 12
Rat 7 322 8q32 Xcr1 X-C motif chemokine receptor 1
Previous and Unofficial Names Click here for help
GPR5 [6,11] | CCXCR1 | chemokine XC receptor 1 | C motif-1/lymphotactin receptor
Database Links Click here for help
Specialist databases
GPCRdb xcr1_human (Hs), xcr1_mouse (Mm)
Other databases
Alphafold P46094 (Hs), Q9R0M1 (Mm)
ChEMBL Target CHEMBL4339 (Hs)
Ensembl Gene ENSG00000173578 (Hs), ENSMUSG00000060509 (Mm), ENSRNOG00000006620 (Rn)
Entrez Gene 2829 (Hs), 23832 (Mm), 301086 (Rn)
Human Protein Atlas ENSG00000173578 (Hs)
KEGG Gene hsa:2829 (Hs), mmu:23832 (Mm), rno:301086 (Rn)
OMIM 600552 (Hs)
Pharos P46094 (Hs)
RefSeq Nucleotide NM_005283 (Hs), NM_011798 (Mm), NM_001106871 (Rn)
RefSeq Protein NP_005274 (Hs), NP_035928 (Mm), NP_001100341 (Rn)
UniProtKB P46094 (Hs), Q9R0M1 (Mm)
Wikipedia XCR1 (Hs)
Natural/Endogenous Ligands Click here for help
XCL1 {Sp: Human}
XCL2 {Sp: Human}
XCL1 {Sp: Mouse} , XCL1 {Sp: Rat}
Comments: Specificity for the endogenous peptide XCL1 at the chemokine-GPCR interface has been determined [5].

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Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]XCL1 (human) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 8.0 pKd 11
⤷ pKd 8.0 [11]
XCL1 {Sp: Human} Peptide Ligand is endogenous in the given species Immunopharmacology Ligand Hs Agonist ~7.3 pEC50 4
⤷ pEC50 ~7.3 (EC50 ~5x10-8 M) [4]
Description: Measuring Ca2+ flux
XCL2 {Sp: Human} Peptide Ligand is endogenous in the given species Immunopharmacology Ligand Hs Agonist ~7.3 pEC50 4
⤷ pEC50 ~7.3 (EC50 ~5x10-8 M) [4]
Description: Measuring Ca2+ flux
Immunopharmacology Comments
XCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. XCR1 is expressed by a subset of dendritic cells [8] and along with its ligand 3647 (lymphotactin), is important for dendritic-cell-mediated cytotoxic immune responses and for the induction of self-tolerance and generation of Treg cells in the thymus.
Cell Type Associations
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   CD141-positive myeloid dendritic cell (CL:0002394)
Comment:  Human XCR1 is expressed exclusively in CD141+ (BDCA3+) DCs, and in mouse expression is restricted to CD8+ DCs which are phenotypically similar to the human cells. XCR1 is NOT expressed in T cells, B cells, NK cells, granulocytes, monocytes, or other DC subsets.
References:  1,3,8
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Calcium channel
References:  11
Tissue Distribution Click here for help
Placenta > spleen, thymus > peripheral blood leukocytes.
Species:  Human
Technique:  Northern blotting.
References:  11
Placenta > thymus > spleen > fetal thymus > fetal spleen > peripheral blood leukocytes > lymph node > bone marrow.
Species:  Human
Technique:  Dot blot.
References:  9
Neutrophils and T lymphocytes.
Species:  Mouse
Technique:  RT-PCR.
References:  2,7
B lymphocytes.
Species:  Mouse
Technique:  RT-PCR.
References:  7
Spleen, lung.
Species:  Mouse
Technique:  Northern blotting.
References:  12
CD8+ cells and NK1.1+ cells.
Species:  Mouse
Technique:  RT-PCR.
References:  12
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of Ca2+ levels in the murine pre-B cell line, L1.2, transfected with the human XCR1 receptor.
Species:  Human
Tissue:  L1.2 cells.
Response measured:  Ca2+ mobilisation.
References:  11
Measurement of chemotaxis of the murine pre-B cell line, L1.2, transfected with the human XCR1 receptor.
Species:  Human
Tissue:  L1.2 cells.
Response measured:  Chemotaxis.
References:  11
Measurement of Ca2+ levels in the murine pre-B cell line, B300-19, transfected with the mouse XCR1 receptor.
Species:  Mouse
Tissue:  B300-19 cells.
Response measured:  Ca2+ mobilisation.
References:  12
Measurement of chemotaxis of the murine pre-B cell line, B300-19, transfected with the mouse XCR1 receptor.
Species:  Mouse
Tissue:  B300-19 cells.
Response measured:  Chemotaxis.
References:  12
Measurement of chemotaxis of T and B lymphocytes and neutrophils endogenously expressing the XCR1 receptor.
Species:  Mouse
Tissue:  T and B lymphocytes, neutrophils.
Response measured:  Chemotaxis.
References:  7
Physiological Functions Click here for help
Chemotaxis.
Species:  Mouse
Tissue:  T and B lymphocytes, neutrophils.
References:  7
Recruitment of mononuclear cells to the rheumatoid arthritic joint.
Species:  Human
Tissue:  Synovial fluid of the rheumatoid joint.
References:  10
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Xcr1tm1Dgen Xcr1tm1Dgen/Xcr1tm1Dgen
B6.129P2-Xcr1/J		 MGI:1346338  MP:0002376 abnormal dendritic cell physiology PMID: 19913446 
Xcr1tm1Dgen Xcr1tm1Dgen/Xcr1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1346338  MP:0002169 no abnormal phenotype detected

References

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1. Bachem A, Güttler S, Hartung E, Ebstein F, Schaefer M, Tannert A, Salama A, Movassaghi K, Opitz C, Mages HW et al.. (2010) Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. J Exp Med, 207 (6): 1273-81. [PMID:20479115]

2. Cairns CM, Gordon JR, Li F, Baca-Estrada ME, Moyana T, Xiang J. (2001) Lymphotactin expression by engineered myeloma cells drives tumor regression: mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor. J Immunol, 167 (1): 57-65. [PMID:11418632]

3. Crozat K, Guiton R, Contreras V, Feuillet V, Dutertre CA, Ventre E, Vu Manh TP, Baranek T, Storset AK, Marvel J et al.. (2010) The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells. J Exp Med, 207 (6): 1283-92. [PMID:20479118]

4. Fox JC, Nakayama T, Tyler RC, Sander TL, Yoshie O, Volkman BF. (2015) Structural and agonist properties of XCL2, the other member of the C-chemokine subfamily. Cytokine, 71 (2): 302-11. [PMID:25497737]

5. Fox JC, Thomas MA, Dishman AF, Larsen O, Nakayama T, Yoshie O, Rosenkilde MM, Volkman BF. (2019) Structure-function guided modeling of chemokine-GPCR specificity for the chemokine XCL1 and its receptor XCR1. Sci Signal, 12 (597). [PMID:31481523]

6. Heiber M, Docherty JM, Shah G, Nguyen T, Cheng R, Heng HH, Marchese A, Tsui LC, Shi X, George SR et al.. (1995) Isolation of three novel human genes encoding G protein-coupled receptors. DNA Cell Biol, 14 (1): 25-35. [PMID:7832990]

7. Huang H, Li F, Cairns CM, Gordon JR, Xiang J. (2001) Neutrophils and B cells express XCR1 receptor and chemotactically respond to lymphotactin. Biochem Biophys Res Commun, 281 (2): 378-82. [PMID:11181058]

8. Lei Y, Takahama Y. (2012) XCL1 and XCR1 in the immune system. Microbes Infect, 14 (3): 262-7. [PMID:22100876]

9. Shan L, Qiao X, Oldham E, Catron D, Kaminski H, Lundell D, Zlotnik A, Gustafson E, Hedrick JA. (2000) Identification of viral macrophage inflammatory protein (vMIP)-II as a ligand for GPR5/XCR1. Biochem Biophys Res Commun, 268: 938-941. [PMID:10679309]

10. Stemmler S, Arinir U, Klein W, Rohde G, Hoffjan S, Wirkus N, Reinitz-Rademacher K, Bufe A, Schultze-Werninghaus G, Epplen JT. (2005) Association of interleukin-8 receptor alpha polymorphisms with chronic obstructive pulmonary disease and asthma. Genes Immun, 6: 225-230. [PMID:15772681]

11. Yoshida T, Imai T, Kakizaki M, Nishimura M, Takagi S, Yoshie O. (1998) Identification of single C motif-1/lymphotactin receptor XCR1. J Biol Chem, 273 (26): 16551-4. [PMID:9632725]

12. Yoshida T, Izawa D, Nakayama T, Nakahara K, Kakizaki M, Imai T, Suzuki R, Miyasaka M, Yoshie O. (1999) Molecular cloning of mXCR1, the murine SCM-1/lymphotactin receptor. FEBS Lett, 458 (1): 37-40. [PMID:10518929]

Contributors

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